A Facile Approach to the Synthesis of 3-(6-Chloro-thiazolo[5,4-b]pyridin-2-ylmethoxy)-2,6-difluoro-benzamide (PC190723)

Zi-Chun Ding; Weicheng Zhou; Xiang Ma

doi:10.1055/s-0031-1290777

Synlett, Table of Contents

Synlett 2012; 23(7): 1039-1042
DOI: 10.1055/s-0031-1290777

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A Facile Approach to the Synthesis of 3-(6-Chloro-thiazolo[5,4-b]pyridin-2-ylmethoxy)-2,6-difluoro-benzamide (PC190723)

Zi-Chun Ding

^aState Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives, Shanghai Institute of Pharmaceutical Industry, State Institute of Pharmaceutical Industry, 1111 North Zhongshan No.1 Rd, Shanghai 200437, P. R. of China

,

Weicheng Zhou

^aState Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives, Shanghai Institute of Pharmaceutical Industry, State Institute of Pharmaceutical Industry, 1111 North Zhongshan No.1 Rd, Shanghai 200437, P. R. of China

,

Xiang Ma*

^aState Key Lab of New Drug & Pharmaceutical Process, Shanghai Key Lab of Anti-Infectives, Shanghai Institute of Pharmaceutical Industry, State Institute of Pharmaceutical Industry, 1111 North Zhongshan No.1 Rd, Shanghai 200437, P. R. of China

^bSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, P. R. of China, Fax: +86(27)83692750 Email: maxwellcn@yahoo.com

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Abstract

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Abstract

Practical synthesis of PC 190723, a bacterial cell division protein Ftsz inhibitor, has been achieved in a high overall yield of 45% in six steps from commercially available starting materials.

Key words

antibacterial agents - cell division inhibitors - thiazolo[5,4-b]pyridine - FtsZ

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References

References and Notes

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5a Haydon DJ, Bennett JM, Brown D, Collins I, Galbraith G, Lancett P, Macdonald R, Stokes NR, Chauhan PK, Sutariya JK, Nayal N, Srivastava A, Beanland J, Hall R, Henstock V, Noula C, Rockley C, Czaplewski L. J. Med. Chem. 2010; 53: 3927
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9 Analytical and spectral data: beige solid; mp 166–168 °C; ¹H NMR (400 MHz, CDCl₃): δ = 6.29 (d, J = 9.2 Hz, 1 H), 7.43 (d, J = 9.6 Hz, 1 H), 14.10 (s, 1 H), 15.00 (br s, 1 H); MS (ESI): m/z = 203.04 [M + Na]⁺; HRMS (ESI): m/z [M⁺ + Na]⁺ calcd for C₇H₄N₂O₄: 203.0069; found: 203.0070
10 Analytical and spectral data: yellow solid; mp 220–222 °C; ¹H NMR (400 MHz, DMSO-d ₆): δ = 5.72 (s, 2 H), 7.10 (td, J = 9.0, 2.0 Hz, 1 H), 7.41 (td, J = 9.2, 5.2 Hz, 1 H), 7.81 (br s, 1 H), 8.10 (br s, 1 H), 8.65 (d, J = 2.4 Hz, 1 H), 8.72 (d, J = 2.0 Hz, 1 H); MS (ESI): m/z = 378.04 [M + Na]⁺, 394.02 [M + K]⁺. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 170.85, 161.12, 155.67, 152.83 (dd, J = 240.35, 6.3 Hz), 148.33 (dd, J = 247.95, 9.6 Hz), 146.20, 145.95, 141.97 (dd, J = 11.2, 3.3 Hz), 129.92, 129.36, 117.16–116.71 (m), 111.32 (d, J = 4.2 Hz), 111.09 (d, J = 3.2 Hz), 69.29; ¹⁹F NMR (500 MHz, DMSO-d ₆): δ = –122.78 (dd, J = 10.0, 5.0 Hz, 6-F), –133.55 (d, J = 10.0 Hz, 2-F); MS (ESI): m/z = 378.04 [M + Na]⁺, 394.02 [M + K]⁺; HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₈ClF₂N₃O₂S: 377.9892; found: 377.9895

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